protein physics lecture 24-25
DESCRIPTION
PROTEIN PHYSICS LECTURE 24-25. PROTEIN STRUCTURE AT ACTION: BIND TRANSFORM RELEASE. BIND: repressors. - turn - . Zn- fingers. DNA & RNA BINDING. Leu-zipper. BIND RELEASE: REPRESSOR. -BINDING-INDUCED DEFORMATION MAKES REPRESSOR ACTIVE, and IT BINDS TO DNA. - PowerPoint PPT PresentationTRANSCRIPT
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PROTEIN PHYSICSPROTEIN PHYSICS
LECTURE 24-25LECTURE 24-25
PROTEIN STRUCTURE AT ACTION:PROTEIN STRUCTURE AT ACTION:
BIND BIND TRANSFORM TRANSFORM RELEASE RELEASE
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BIND: repressorsBIND: repressors
-- turnturn --
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DNA & RNADNA & RNABINDINGBINDING
Zn-Zn-fingersfingers
Leu-zipperLeu-zipper
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-BINDING-INDUCED DEFORMATION -BINDING-INDUCED DEFORMATION MAKES REPRESSOR ACTIVE, and IT BINDS TO DNAMAKES REPRESSOR ACTIVE, and IT BINDS TO DNA
BIND BIND RELEASE: RELEASE: REPRESSOR
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ImmunoglobulinImmunoglobulin
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Standard positions of active sites Standard positions of active sites in protein foldsin protein folds
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There are some There are some with catalytic with catalytic (Ser-protease) site(Ser-protease) site
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Preferential binding of TS: Preferential binding of TS: RIGID RIGID enzymeenzyme
CatalysisCatalysis:: stabilization of the transition state stabilization of the transition state (TS) (TS)
Theory: Pauling & HoldenTheory: Pauling & Holden
BINDBIND TRANSFORM TRANSFORM RELEASERELEASE
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Catalysis: stabilization of the transition stateCatalysis: stabilization of the transition state (TS) (TS)
Theory: Pauling & HoldenTheory: Pauling & HoldenExperimental verification: FershtExperimental verification: Fersht
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PP
reputedreputedTSTS
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Catalysis: stabilization of the transition stateCatalysis: stabilization of the transition state (TS) (TS)
Theory: Pauling & HoldenTheory: Pauling & HoldenExperimental verification: FershtExperimental verification: Fersht
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PP
reputedreputedTSTS
This This proteinproteinengineeringengineeringreducesreducesthe ratethe rateby 1000000by 1000000
PreferentialPreferentialbinding binding of TS:of TS:RIGIDRIGID
enzymeenzyme
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Catalytic antibodiesCatalytic antibodies ABZYM = AABZYM = AntyntyBBodyody enenZYMZYM
AntibodiesAntibodiesare are
selectedselectedto TS-liketo TS-likemoleculemolecule
Transition state (TS)Transition state (TS)
PreferentialPreferentialbinding binding of TS:of TS:RIGIDRIGID
enzymeenzyme
BIND BIND TRANSFORMTRANSFORM RELEASE RELEASE
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BIND BIND TRANSFORM TRANSFORM RELEASE RELEASE:: ENZYME
Note: small active site
chymotrypsinchymotrypsin
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SometimesSometimes::
Different folds with the same active site: Different folds with the same active site: the same biochemical functionthe same biochemical function
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POST-TRANSLATIONAL MODIFICATIONPOST-TRANSLATIONAL MODIFICATION
Sometimes, Sometimes, only theonly the CHAIN CUT-INDUCED DEFORMATION CHAIN CUT-INDUCED DEFORMATION MAKES THE ENZYME ACTIVE READYMAKES THE ENZYME ACTIVE READY
ChymotripsinoChymotripsinogengen
active cat. site
non-active “cat. site” CUT
ChymotripsinChymotripsin
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Chymotrypsin catalyses hydrolysis of a peptide Chymotrypsin catalyses hydrolysis of a peptide
Spontaneous hydrolysis: very slowSpontaneous hydrolysis: very slow
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SER-protease: SER-protease: catalysiscatalysis
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CHYMOTRYPSIN ACTIVE SITECHYMOTRYPSIN ACTIVE SITE with with INHIBITOR INHIBITOR
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Preferential binding of TS: Preferential binding of TS: RIGID RIGID enzymeenzyme
F F = = kk11xx11 = - = - kk22xx22 E Ei i = (= (kkii /2/2)()(xxii))22 = = FF22//((2k2kii ))Hooke’s & 2-nd Newton’s Energy is concentrated Hooke’s & 2-nd Newton’s Energy is concentrated laws in the laws in the softersofter body. body. Effective catalysis: when Effective catalysis: when substrate is softer than substrate is softer than proteinprotein
Kinetic energy Kinetic energy cannot be stored cannot be stored for catalysisfor catalysisFriction stops a molecule within Friction stops a molecule within picoseconds: picoseconds:
m(dv/dt) = -(3m(dv/dt) = -(3DD)v )v [Stokes law][Stokes law]D – diameter; m ~ DD – diameter; m ~ D33 – mass; – mass; – viscosity – viscosity
ttkinetkinet 10 10-13 -13 sec sec (D/nm) (D/nm)22 in waterin water
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PROTEIN STRUCTURE AT ACTION:PROTEIN STRUCTURE AT ACTION:
BIND BIND TRANSFORM TRANSFORM RELEASE RELEASE
RIGID CATALITIC SITERIGID CATALITIC SITE
INDEPENDENT ON OVERALL CHAIN FOLDINDEPENDENT ON OVERALL CHAIN FOLD
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MOTIONSMOTIONS
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Double sieve:Double sieve: movement of substrate movement of substrate
from one active site to anotherfrom one active site to another
tRNAtRNAIleIle
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Movement in two-domain enzyme: Movement in two-domain enzyme: One conformation for binding (and release),One conformation for binding (and release),
another for catalysisanother for catalysis
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Two-domain dehydrogenases: Two-domain dehydrogenases: Universal NAD-binding domain;Universal NAD-binding domain;
Individual substrate-binding domainIndividual substrate-binding domain
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Movement in quaternary structure: Movement in quaternary structure: Hemoglobin vs. myoglobinHemoglobin vs. myoglobin
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Механохимический цикл
МиозинМиозин АктинАктин
АТФ АДФ + Ф15 ккал/мольв клеточных
условиях
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Mechanochemical cycleMechanochemical cycle
MyosinMyosin
ActinActin
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SUMMARYSUMMARY
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PROTEIN PHYSICSPROTEIN PHYSICS
InteractionsInteractions
StructuresStructures
SelectionSelection
States & States & transitionstransitions
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Intermediates Intermediates & nuclei& nuclei
Structure Structure prediction & prediction & bioinformaticsbioinformatics
Protein Protein engineering & engineering & designdesign
Functioning Functioning